Chronic Recurrent Multifocal Osteomyelitis Patients Research Articles

OP0006 A Large National Cohort of French Patients with Chronic Recurrent Multifocal Osteitis

BackgroundFrequency of chronic recurrent multifocal osteomyelitis (CRMO), also known as nonbacterial osteomyelitis, seems to be underestimated and often leads to consequential residual impairments.ObjectivesThe aim of this study was to collect...

Attenuated TLR4/MAPK signaling in monocytes from patients with CRMO results in impaired IL-10 expression

Chronic recurrent multifocal osteomyelitis (CRMO) is an autoinflammatory bone disorder of unknown origin. We previously demonstrated that monocytes from CRMO patients fail to express the immune-modulatory cytokine interleukin-10 (IL-10) in a chromatin dependent manner. Here, we demonstrate that attenuated extracellular-signal regulated kinase (ERK)1 and 2 signaling in response to TLR4 activation results in failure to induce IL-10 expression in monocytes from CRMO patients. Attenuated ERK1/2 activation results in 1) reduced levels of Sp-1, a transcription factor that induces IL-10 expression in monocytes, and 2) impaired H3S10 phosphorylation of the IL10 promoter, an activating epigenetic mark. The pro-inflammatory cytokines tumor necrosis factor (TNF)α and IL-6 are not negatively affected, resulting in an imbalance towards pro-inflammatory cytokines. Thus, impaired ERK1/2 signaling with subsequently reduced Sp-1 expression and H3S10 phosphorylation of the IL10 promoter may centrally contribute to the pathophysiology of CRMO.

Comparative cytokine analysis across a spectrum of genetically and/or clinically defined auto-inflammatory syndromes

Background/purposeAuto-inflammatory diseases constitute a group of disorders that manifest systemic inflammation in the absence of infection, auto-antibodies or auto-reactive T cells. A specific genetic mutation is identified in some of...

Dramatic pain relief and resolution of bone inflammation following pamidronate in 9 pediatric patients with persistent chronic recurrent multifocal osteomyelitis (CRMO)

BackgroundChronic recurrent multifocal osteomyelitis (CRMO) is an inflammatory, non-infectious osteopathy that affects predominantly patients ≤ 18 years of age. There is no uniformly effective treatment. Our objective is to describe clinical, magnetic resonance imaging (MRI), and bone resorption response to intravenous pamidronate in pediatric CRMO.MethodsWe report our prospectively documented experience with all CRMO patients treated with pamidronate between 2003 and 2008 at a tertiary pediatric centre. Pamidronate was administered as intravenous cycles. The dose of pamidronate varied among subjects but was given as monthly to every 3 monthly cycles depending on the distance the patient lived from the infusion center. Maximum cumulative dose was ≤ 11.5 mg/kg/year. Pamidronate treatment was continued until resolution of MRI documented bone inflammation. Visual analog scale for pain (VAS) and bone resorption marker urine N-telopeptide/urine creatinine (uNTX/uCr) were measured at baseline, preceding each subsequent pamidronate treatment, at final follow-up, and/or at time of MRI confirmed CRMO flare. MRI of the affected site(s) was obtained at baseline, preceding every 2nd treatment, and with suspected CRMO recurrence.ResultsNine patients (5 F: 4 M) were treated, with a median (range) age at treatment of 12.9 (4.5–16.3) years, and median (range) duration of symptoms of 18 (6–36) months. VAS decreased from 10/10 to 0–3/10 by the end of first 3–day treatment for all patients. The mean (range) time to complete MRI resolution of bone inflammation was 6.0 (2–12) months. The mean (confidence interval (CI)) baseline uNTX/uCr was 738.83 (CI 464.25, 1013.42)nmol/mmol/creatinine and the mean (CI) decrease from baseline to pamidronate discontinuation was 522.17 (CI 299.77, 744.56)nmol/mmol/creatinine. Median (range) of follow-up was 31.4 (24–54) months. Four patients had MRI confirmed CRMO recurrence, which responded to one pamidronate re-treatment. The mean (range) uNTX/uCr change as a monthly rate from the time of pamidronate discontinuation to flare was 9.41 (1.38–19.85)nmol/mmol/creatinine compared to -29.88 (-96.83–2.01)nmol/mmol/creatinine for patients who did not flare by the time of final follow-up.ConclusionPamidronate resulted in resolution of pain and MRI documented inflammation in all patients. No patient flared while his/her uNTX/uCr remained suppressed. We propose that pamidronate is an effective second-line therapy in persistent CRMO.

Current Diagnosis and Treatment of Spondylodiscitis: Differential Diagnosis

It would have been necessary to describe and specify the differential diagnosis, particularly as it proved to be impossible to avoid the clinically confusing ambiguity of this diagnosis in the title. The underlying problem was the assumption that the terms and also generally and exclusively imply bacterial or purulent pathogenesis and morphology, so that no other terms are needed for postinfectious (secondary) chronicity. This ignores the fact that non-bacterial (aseptic and sterile) osteomyelitis, spondylitis, and spondylodiscitis exist—as rheumatologists have known for many years. In particular, has been recognized, at least since its detailed description in 1973 (1), as a noninfectious and nonbacterial symptom of Bechterew’s disease and of spondyloarthritis (also known as spondyloarthropathy). This frequent and destructive complication is observed in affected motor segments of the spinal column and involves perivertebral tendinopathy. We identified abacterial as primary osteomyelitis in chronic recurrent multifocal osteomyelitis (CRMO) as an entity in patients of all ages. It was differentiated as part of the symptom spectrum of the „SAPHO syndrome“ (www.sapho-syndrom-crmo.de and Orphanet 2004, n ≥173). It has then been subjected to interdisciplinary analysis and the aseptic clinical course of the osteitis has been described as a plasma cell sclerotic process in three steps (2). About a third of all CRMO patients in all age groups develop clinically relevant involvement of the vertebral bodies. These cases of sterile spondylitis can then progress to spondylodiscitis. Thus CRMO is an important differential diagnosis for ankylosing spondylarthritis and one which has largely been ignored (3).